1. Field of the Invention
The present invention relates to a liposome composition and a method for producing the same. The present invention relates to a liposome composition which can be preferably used for pharmaceutical applications and a method for producing the same.
2. Description of the Related Art
A liposome (hereinafter, also referred to as lipid vesicle) is a closed vesicle formed of a lipid bilayer membrane using lipids, and has a water phase (inner water phase) within the space of the closed vesicle. Liposomes are usually present in a state of being dispersed in an aqueous solution (outer water phase) outside the closed vesicle. Liposomes have been studied for a variety of applications such as immune sensors, artificial red blood cells, and carriers of drug delivery systems taking advantage of features such as barrier capacity, compound retention capacity, biocompatibility, the degree of freedom of setting the particle size, ready biodegradability, and surface-modifying properties. In carrier applications, liposomes can encapsulate water-soluble compounds, lipophilic low-molecular weight materials, polymers and a wide range of materials.
In the case where liposomes are used particularly as a carrier for a drug delivery system, it is necessary to make a particle size to be about 200 nm or less in terms of permeation through a biological membrane. Further, in a carrier for a drug delivery system, it is also necessary to have liposomes which form particles having a good dispersibility under the temperature conditions of about 37° C. which is the body temperature of a mammal. In particular, with regard to nano-sized fine particles, it is preferred to impart preservation stability from various viewpoints such as aggregation, precipitation, and leakage of drugs.
As a carrier for a drug delivery system, in the case where a drug (solution or the like containing liposomes containing a drug) is administered by intravenous injection, high safety is required for an intravenous injection product. Additives such as chlorinated solvents, for example chloroform, or dispersing aids whose use are not allowed are undesirable. In addition, impartment of stability to a pharmaceutical product is also necessary, and correspondingly suppression of drug leakage, lipid decomposition or the like after storage is required. Further, suitability for sterile filtration is also required in order to guarantee sterility. When it is desired to produce liposomes as a pharmaceutical product on an industrial scale, it is necessary to take into account the requirements as described above.
WO2005/021012A discloses a gemcitabine-encapsulating pharmaceutical carrier which is capable of suppressing a release rate of gemcitabine and is capable of maintaining a local concentration of gemcitabine for a long period of time. Further, this patent document discloses that a suitable release rate is exhibited by cholesterols being contained as membrane components in a specific proportion. Further, this patent document discloses a drug carrier containing gemcitabine-encapsulated liposomes in a carrier containing cholesterols in a proportion of 0 mol % or more and less than 35 mol %, together with phospholipids. Further, this patent document also discloses that the release rate of a drug from liposomes declines as the proportion of cholesterol decreases.
JP4971142B discloses an aqueous solution containing liposomes in an aqueous medium, where each liposome has an aqueous internal space isolated from the medium by a membrane containing cholesterol and phosphatidylcholine, and the internal space contains supplementary irinotecan and sucrose octasulfate. Further, although this liposome composition allows a sufficiently high intraliposomal osmotic pressure of 727 mmol/kg, there may be a case where drugs that can be used in the liposomes are limited because the Examples use polyanions such as sucrose octasulfate. Further, Example 64 describes the preparation of an aqueous solution having an osmotic pressure of 727 mmol/kg. However, there is no mention of preservation stability or releasability of this aqueous solution.
In all of the above-mentioned documents, a liposome composition having a practically required long-term preservation stability and also having a suitable release rate and a method for producing the same have not been fully established, and correspondingly improvements are desired.